• 제목/요약/키워드: aAntiviral

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The Synthesis of the Stable IVDU Derivative for Imaging HSV-1 TK Expression (체내 안정형 HSV1-tk (Herpes Simplex Virus Type-1 Thymidine Kinase) 영상용 IVDU 유도체의 합성)

  • Kim, Eun-Jung;Choi, Tae-Hyun;Ahn, Soon-Hyuk;Kim, Byoung-Soo;Park, Hyun;Cheon, Gi-Jeong;Rhee, Hak-June;An, Gwang-Il
    • Nuclear Medicine and Molecular Imaging
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    • v.43 no.5
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    • pp.478-486
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    • 2009
  • Purpose: 5-iododeoxyuridine analogues have been exclusively developed for the potential antiviral and antitumor therapeutic agents. In this study, we synthesized carbocyclic radioiododeoxyuridineanalogue (ddIVDU) and carbocyclic intermediate as efficient carbocyclic radiopharmaceuticals. Materials and Methods: The synthesis is LAH reduction, hetero Diels-Alder reaction as key reactions including Pd(0)-catalyzed coupling reaction together with organotin. MCA-RH7777 (MCA) and MCA-tk (HSV1-tk positive) cells were treated with various concentration of carbocyclic ddIVDU, and GCV. Cytotoxicity was measured by the MTS methods. For in vitro uptake study, MCA and MCA-tk cells were incubated with 1uCi of [$^{125}I$]carbocyclic ddIVDU. Accumulated radioactivity was measured after various incubation times. Results: The synthesis of ddIVDU and precursor for radioiodination were achieved from cyclopentadiene in good overall yield, respectively. The radioiododemetallation for radiolabeling gave more than 80% yield with > 95% radiochemical purity. GCV was more toxic than carbocyclic ddIVDU in MCA-tk cells. Accumulation of [$^{125}I$]carbocyclic ddIVDU was higher in MCA-tk cells than MCA cells. Conclusion: Biological data reveal that ddIVDU is stable in vitro, less toxic than ganciclovir (GCV), and selective in HSV1-tk expressed cells. Thus, this new carbocyclic nucleoside, referred to in this paper as carbocyclic 2',3'-didehydro-2',3'-dideoxy-5- iodovinyluridine (carbocyclic ddIVDU), is a potential imaging probe for HSV1-tk.

Deterimination of an Optimal Time Point for Analyzing Transcriptional Activity and Analysis of Transcripts of Avian Influenza Virus H9N2 in Cultured Cell (배양세포에서 Semi-quantitative RT-PCR에 의한 조류인플루엔자 H9N2의 전사활성 분석 최적 시기 결정 및 전사체 분석)

  • Na, Gi-Youn;Lee, Young-Min;Byun, Sung-June;Jeon, Ik-Soo;Park, Jong-Hyeon;Cho, In-Soo;Joo, Yi-Seok;Lee, Yun-Jung;Kwon, Jun-Hun;Koo, Yong-Bum
    • Korean Journal of Microbiology
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    • v.45 no.3
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    • pp.286-290
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    • 2009
  • The transcription of mRNA of avian influenza virus is regulated temporally during infection. Therefore, the measurement of transcript level in host cells should be performed before viral release from host cells because errors can occur in the analysis of the transcript levels if the viruses released from the infected cells re-infect cells. In this study, the timing of viral release was determined by measuring the level of viral RNA from viruses released from H9N2-infected chicken fibroblast cell line UMNSAH/DF-1 by semi-quantitative RT-PCR. The viral genomic RNA was isolated together with mouse total RNA which was added to the collected medium as carrier to monitor the viral RNA recovery and to use its GAPDH as an internal control for normalizing reverse transcription reaction as well as PCR reaction. It was found that viral release of H9N2 in the chicken fibroblast cell line UMNSAH/DF-1 took between 16 and 20 h after infection. We measured all 8 viral mRNA levels. Of the 8 transcripts, 7 species of viral mRNAs (each encoding HA, NA, PB1, PB2, NP, M, NS, respectively) except PA mRNA showed robust amplification, indicating these mRNA can be used as targets for amplification to measure transcript levels. These results altogether suggest that the method in this study can be used for screening antiviral materials against viral RNA polymerase as a therapeutic target.

Trends of mushroom science and mushroom industry (버섯과학과 버섯산업의 동향)

  • Yoo, Young-Bok;Kong, Won-Sik;Oh, Se-Jong;Cheong, Jong-Chun;Jang, Kab-Yeul;Jhune, Chang-Sung
    • Journal of Mushroom
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    • v.3 no.1
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    • pp.1-23
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    • 2005
  • World production of mushrooms has been increasing 10-20% every year. Recently, Pleurotus eryngii and P. nebrodensis are very popular as new mushroom species for cultivation. Two kinds of mushrooms, Gumji (Ganoderma) and Soji, were described in old book of Samguksagi (History of the three kingdoms; 1145) in Koryo-dynasty. Many kinds of mushrooms were also described in more than 16 kinds of old books during Chosun-dynasty in Korea. One hundred and sixty commercial strains of 25 species in mushrooms were distributed to cultivators. By the way, only 8 varieties of them have registered variety protection. Mushroom industry as important export products developed from 1960 to 1980. Production of mushrooms as food was 181,828 metric tons valued at 800 billion Korean won in 2003. Isolated and identified substances from mushrooms are promising antifungal, antiinflammatory, antitumor, antiviral (anti-HIV), antibacterial & antiparasitic, antidiabetic, immunomodulating, kidney tonic, hepatoprotective, nerve tonic, and sexual potentiator. These substances can also be used for blood pressure regulation and effective against cardiovascular disorders, hypocholesterolemia & hyperlipidemia, and chronicbronchitis. Mushroom products including pharmaceuticals, tonics, healthy beverages, functional biotransformants, and processed foods have also became available on the markets. Compost and feed can likewise be made from mushroom substrates after harvest. The mushroom industry is already one of the fastest growing investment sectors in Korea. By the way, there is a need to strain improvement for variety protection, advanced cultivation technology at low cost for growers, and control of demand and supply for marketing in order to more upgrade development of mushroom industry in the future.

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Inhibitory Effect on Infection of Plant Viruses by Filtrate Powder from Culture Broth of Acinetobacter sp. and Its Mode of Action (Acinetobacter sp. 배양여과액 분말제제의 식물바이러스에 대한 감염억제 효과 및 작용)

  • Kim Mi-Soon;Jung Min-Young;Kim Yun-Sung;Jang Cheol;Hwang In-Cheon;Ryu Ki-Hyun;Choi Jang-Kyung
    • Research in Plant Disease
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    • v.12 no.2
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    • pp.91-98
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    • 2006
  • A filtrate powder, designated as KNF2022, produced from culture broth of Acinetobacter sp. KTB3 was tested for their inhibitory effects on Pepper mild mottle virus (PMMoV) infection to Nicotiana glutinosa or N. tabacum cv. Xanthi nc. When 1/100 dilution with distilled water was treated to the plants and PMMoV was inoculated, the inhibition was estimated to be 94.3 and 95.6%, respectively. The same concentrations of KNF2022 inhibited infections of Pepper mottle virus (PepMoV) and Cucumber mosaic virus (CMV) on Chenopodium amaranticolor by 97.1 and 92.5%, respectively. Duration of inhibitory activity of the filtrate powder from Acinetobacter sp. culture broth against PMMoV infection on N. glutinosa was maintained for 2 days at 80% inhibition level, however, the inhibitory effect was diminished from 4 days after treatment to 50% levels. To evaluate inhibitory effects on systemic host plants of the antiviral agent, symptom developments of PMMoV, PepMoV and CMV on KNF2022-treated pepper plants were investigated. Delayed symptom developments until 10 days after inoculation (DAI) were observed for all the three viruses when the viruses were inoculated individually, and these delayed symptom development effects were maintained until 30 DAI in case of PepMoV. Moreover, PepMoV was not detected by RT-PCR and ELISA until 30 DAI. These delayed symptom development effects were diminished in all combinations of three virus co-inoculations due to synergism of three viruses on symptom developments. Inhibitory effect of KNF2022 was verified under electron microscopic examinations using purified virus preparations. Particles of PMMoV and PepMoV were observed on specimens from 5 min after KNF2022 treatment, and the particle sizes were reached in the range of 200-250 nm and 400-600 nm, respectively. Furthermore, the viral particles were destructed and particle sizes were reached in the range of 100-150 nm and 300-500 nm, respectively, on 60 min after treatments. Reduction of local lesion numbers on N. tabacum cv. Xanthi nc and C. amaranticolor were accompanied with reduction of virus particle sizes. In the case of CMV destructed particle numbers were also increased according to incubation period after KNF2022 treatment and local lesions on C. amaranticolor were reduced.

Development and Research into Functional Foods from Hydrolyzed Whey Protein Powder with Sialic Acid as Its Index Component - I. Repeated 90-day Oral Administration Toxicity Test using Rats Administered Hydrolyzed Whey Protein Powder containing Normal Concentration of Sialic Acid (7%) with Enzyme Separation Method - (Sialic Acid를 지표성분으로 하는 유청가수분해단백분말의 기능성식품 개발연구 - I. 효소분리로 7% Siailc Acid가 표준적으로 함유된 유청가수분해단백분말(7%)의 랫드를 이용한 90일 반복경구투여 독성시험 평가 연구 -)

  • Noh, Hye-Ji;Cho, Hyang-Hyun;Kim, Hee-Kyong
    • Journal of Dairy Science and Biotechnology
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    • v.34 no.2
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    • pp.99-116
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    • 2016
  • We herein performed animal safety assessment in accordance with Good Laboratory Practice (GLP) regulations with the aim of developing sialic acid from glycomacropeptide (hereafter referred to as "GMP") as an index ingredient and functional component in functional foods. GMP is a type of whey protein derived from milk and a safe food, with multiple functions, such as antiviral activity. A test substance was produced containing 7% (w/w) sialic acid and mostly-hydrolyzed whey protein (hereafter referred to as "7%-GNANA") by enzymatic treatment of substrate GMP. The maximum intake test dose level was selected based on 5,000 mg/kg/day dose set for male NOEL (no-observed-effect-level) and female NOAEL (no-observed-adverse-effect-level) determined by a dose-range finding (DRF) test (GLP Center of Catholic University of Daegu, Report No. 15-NREO-001) that was previously conducted with the same test substance. To evaluate the toxicity of a repeated oral dose of the test substance in connection with the previous DRF study, 1,250, 2,500, and 5,000 mg/kg of the substance were administered by a probe into the stomachs of 6-week-old SPF Sprague-Dawley male and female rats for 90 d. Each test group consisted of 10 male and 10 female rats. To determine the toxicity index, all parameters, such as observation of common signs; measurements of body weight and food consumption; ophthalmic examination; urinalysis, electrolyte, hematological, and serum biochemical examination; measurement of organ weights during autopsy; and visual and histopathological examinations were conducted according to GLP standards. After evaluating the results based on the test toxicity assessment criteria, it was determined that NOAEL of the test substance, 7%-GNANA, was 5,000 mg/kg/day, for both male and female rats. No animal death was noted in any of the test groups, including the control group, during the study period, and there was no significant difference associated with test substance, as compared with the control group, with respect to general symptoms, body weight changes, food consumption, ophthalmic examination, urinalysis, hematological and serum biochemical examination, and electrolyte and blood coagulation tests during the administration period (P<0.05). As assessed by the effects of the test substance on organ weights, food consumption, autopsy, and histopathological safety, change in kidney weight as an indicator of male NOAEL revealed up to 20% kidney weight increase in the high-dose group (5,000 mg/kg/day) compared with the change in the control group. However, it was concluded that this effect of the test substance was minor. In the case of female rats, reduction of food consumption, increase of kidney weight, and decrease of thymus weight were observed in the high-dose group. The kidney weight increased by 10.2% (left) and 8.9% (right) in the high-dose group, with a slight dose-dependency compared with that of the control group. It was observed that the thymus weight decreased by 25.3% in the high-dose group, but it was a minor test substance-associated effect. During the autopsy, botryoid tumor was detected on the ribs of one subject in the high-dose group, but we concluded that the tumor has been caused by a naturally occurring (non-test) substance. Histopathological examination revealed lesions on the kidney, liver, spleen, and other organs in the low-dose test group. Since these lesions were considered a separate phenomenon, or naturally occurring and associated with aging, it was checked whether any target organ showed clear symptoms caused by the test substance. In conclusion, different concentrations of the test substance were fed to rats and, consequently, it was verified that only a minor effect was associated with the test substance in the high-dose (5,000 mg/kg/day) group of both male and female rats, without any other significant effects associated with the test substance. Therefore, it was concluded that NOAEL of 7%-GNANA (product name: Helicobactrol) with male and female rats as test animals was 5,000 mg/kg/day, and it thus was determined that the substance is safe for the ultimate use as an ingredient of health functional foods.

Clinical Analysis of Acute Respiratory Tract Infections by Influenza Virus in Children (인플루엔자 바이러스에 의한 소아 급성 호흡기 감염증의 유행 및 임상 양상)

  • Kwon, Min Kyoung;Kim, Mi Ran;Park, Eun Young;Lee, Kon Hee;Yoon, Hae Sun;Kim, Kwang Nam;Lee, Kyu Man
    • Clinical and Experimental Pediatrics
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    • v.45 no.12
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    • pp.1519-1527
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    • 2002
  • Purpose : Although influenza virus is one of the most important causes of acute respiratory tract infections(ARTIs) in children, virus isolation is not popular and there are only a few clinical studies on influenza in Korea. We evaluated the epidemiologic and clinical features of ARTIs by influenza virus in children. Methods : From February 1995 to August 2001, nasopharyngeal aspirations were obtained and cultured for the isolation of influenza virus in children admitted with ARTIs. The medical records of patients with influenza virus infection were reviewed retrospectively. Results : Respiratory viruses were isolated in 997(22.0%) out of 4,533 patients examined, and influenza virus was isolated in 164 cases(3.6%). Influenza virus was isolated year after year mainly from December to April of next year. The ratio of male and female was 1.9 : 1 with a median age of 15 months. The most common clinical diagnosis of influenza virus infection was pneumonia, and fever and cough developed in most patients. There was no difference between influenza A and B infection in clinical diagnoses and symptoms. All patients recovered without receiving antiviral treatment except for one patient diagnosed with pneumonia who had underlying disease of Down syndrome with ventricular septal defect. Conclusion : ARTIs caused by influenza virus developed every winter and spring during the period of study. Because fatal complication can develop in the high risk group, prevention, early diagnosis and proper management of influenza should be emphasized.

Clinical Analysis of Influenza in Children and Rapid Antigen Detection Test on First Half of the Year 2004 in Busan (2004 상반기 부산 지역에서 유행한 인플루엔자의 임상 역학적 분석 및 인플루엔자 진단에 있어서의 신속 항원 검사법)

  • Choi, So Young;Lee, Na Young;Kim, Sung Mi;Kim, Gil Heun;Jung, Jin Hwa;Choi, Im Jung;Cho, Kyung Soon
    • Pediatric Infection and Vaccine
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    • v.11 no.2
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    • pp.158-169
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    • 2004
  • Purpose : Although influenza is one of the most important cause of acute respiratory tract infections in children, virus isolation is not popular and there are only a few clinical studies on influenza and diagnostic methods. We evaluated the epidemiological and clinical features of influenza in children and rapid antigen detection test(QuickVue influenza test) on fist half of the year 2004 in Busan. Methods : From January 2004 to June 2004, throat swab and nasal secretion were obtained and cultured for the isolation of influenza virus and tested by rapid antigen detection test(QuickVue influenza test) in children with suspected influenza infections. The medical records of patients with influenza virus infection were reviewed retrospectively. Results : Influenza viruses were isolated in 79(17.2%) out of 621 patients examined. Influenza virus was isolated mainly from March to April 2004. The ratio of male and female with influenza virus infection was 1.2 : 1 with median age of 4 years 6month. The most common clinical diagnosis of influenza virus infection was bronchitis. There was no difference between influenza A and B infection in clinical diagnosis and symptoms. All patients recovered without severe complication. The sensitivity obtained for rapid antigen detection test (QuickVue influenza test) was 93.6% and the specificity was 80.2%, the positive predictive value 40.8%, the negative predictive value 98.8%. Conclusion : With rapid antigen detection test, it is possible early detection of influenza in children. reduction in use of antimicrobial agent and early use of antiviral agent.

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